Coronary heart disease (CHD) is the leading cause of death in women. Observational studies suggest that postmenopausal estrogen replacement therapy (ERT) reduces the risk of a new CHD event by 50% in healthy women, and by 80% in women with prior CHD. Whether the addition of progestin (PERT) to prevent estrogen-induced endometrial cancer alters the risk of CHD. Whether the addition of progestin (PERT) to prevent estrogen-induced endometrial cancer alters the risk of CHD is unknown. The apparent cardioprotective effect of ERT might be real (perhaps mediated by changes in clotting factors or lipids) or it might be due to confounding if, for example, estrogen users are healthier than non-users. To resolve this question, we propose to participate in the Hormone Replacement Study (HRS), a secondary prevention trial, 3,252 postmenopausal women with prior myocardial infarction (M) or angiographically documented coronary disease will be randomized to one of three blinded regimens: ERT(0.625 mg. conjugated estrogen per day), PERT (ERT plus 2.5 mg medroxyprogesterone acetate per day), or placebo. The primary outcome, 6- year incidence of CHD (myocardial infarction or CHD death), offers a power of 0.9 to detect a 37.5% reduction in either hormone group compared to placebo. The trial will also compare adverse event rates, and examine the effects of ERT or PERT on quality of life and lipids in the overall cohort and in the 17% who are Black and the 8% who are Hispanic. HRS brings together leading experts in cardiovascular trials an women's health to build on the experience in PEPI (Postmenopausal Estrogen/Progestin Interventions). Bowman Gray will serve as one of twelve clinical centers with excellent track records in recruitment and follow-up will each randomize at least 260 women and participate in study-wide scientific activities. The coordinating center will organize governance and communication, coordinate design and implementation, create and manage the data and quality control systems, and assure timely analysis and dissemination of findings. The effect of ERT and PERT on CHD is a most important issue for postmenopausal women. If HRS demonstrates that these treatments reduce the risk of recurrent CHD without major adverse effects, it is likely that hormone therapy (now used by about 20% of postmenopausal women in the U.S.) would become much more common and that national CHD rates would decline substantially.